The present invention provides two novel polyhydroxycyclopentane derivatives which have certain valuable biological activities and provides methods of preparing these compounds as well as methods and compositions using them for therapeutic and prophylactic purposes.
The compounds of the present invention are 5-amino-1-(hydroxymethyl)cyclopentane-1,2,3,4-tetraol and 2-amino-4-(hydroxymethyl)-3a,5,6,6a-tetrahydro-4H-cyclopent[d]oxazole-4,5, 6-triol, whose formulae (I) and (II), respectively, are given hereafter. These compounds may be prepared by fermentation or by cleavage of the compound known as trehazolin, which may be represented by the formula (III), shown below. However, 2-amino-4-(hydroxymethyl)-3a,5,6,6a-tetrahydro 4H-cyclopent[d1-oxazole-4,5 ,6-triol and trehazolin both undergo tautomerism, and they may, therefore, also be represented by the formulae (IIa) and (IIIa), respectively, shown below: ##STR1##
It is thought that trehazolin may be the same compound as that named "trehalostatin" in PCT International Publication No. WO 90/10010.
The compounds of the present invention have the ability to inhibit the activity of various sugar hydrolases, and, in particular, .beta.-glucosidase and sucrase.
It has been reported that compounds having a strong inhibitory activity against .beta.-glucosidase, such as castanospermine and deoxynojirimycin, are useful as anti-neoplastic agents and as anti-AIDS (Acquired Immune Deficiency Syndrome) agents [R. A. Gruters et al., Nature, 330, 74-77 (1987); M. J. Humphries et al., Cancer Res., 46, 5215-5222 (1986)]. It is therefore expected that compounds having the ability to inhibit the activity of .beta.-glucosidase will be useful as anti-neoplastic or anti-AIDS agents.
It has also been reported that compounds having a strong inhibitory activity against sucrase, such as AO-128 and Acarbose, are useful as anti-diabetic agents and as anti-obesity agents [Satoshi Horii et al., Journal of Medicinal Chemistry, 29, 1038-1046 (1986); T. Goda et al., Journal of Japanese Society of Food and Nutrition, 34, (2) 134-139 (1981)]. It is therefore expected that compounds having the ability to inhibit the activity of sucrase will be useful for the treatment and prophylaxis of diabetes and obesity.
Compounds having a certain structural resemblance to the compounds of the present invention are:
the mannostatins, described, inter alia. by T. Aoyagi et al. [The Journal of Antibiotics, Vol. XLII No. 6, 883 (1989)], which are said to have the ability to inhibit the activity of .alpha.-D-mannosidase;
(1S, 2R, 3S, 4R, 5R)-methyl[2,3,4-trihydroxy-5-(hydroxymethyl)cyclopentyl]amine, described, inter alia. by R. A. Farr et al. [Tetrahedron Letters, 31, 7109 (I990)], which is also said to have the ability to inhibit the activity of .alpha.-mannosidase;
allosamidin, described, inter alia. by S. Sakuda et [Tetrahedron Letters, 27, 2475 (1986)], which is said to have the ability to inhibit the activity of insect chitinase; and
kifunensine, described, inter alia. by H. Kayakiri et al. [J. Org. Chem., 54, 4015 (1989)], which is said to be an immunomodulator with the ability to inhibit the activity of .alpha.-mannosidase.